1. Field of the Invention
The invention relates to a magnetic resonance diagnostic apparatus which acquires information about relatively insensitive nuclear species, such as .sup.13 C, with high sensitivity.
2. Description of the Related Art
Attention has been paid to the observation of spectra of nuclear species such as .sup.13 C in that information about biochemistry such as metabolism or energy metabolism can be obtained. Assuming the sensitivity of .sup.1 H to be unity, the sensitivity of .sup.13 C is as low as about 1/4. Thus, there arises a problem in that the signal-to-noise ratio becomes very low.
Methods of improving the signal-to-noise ratio by employing large polarization of .sup.1 H have been developed recently, which are roughly classified into two categories: .sup.13 C observation (polarization transfer method) and .sup.1 H observation. .sup.13 C observation methods include INEPT (Insensitive Nuclei Enhanced by Polarization Transfer) methods and DEPT (Distortionless Enhancement by Polarization Transfer) methods. .sup.1 H observation methods include HSQC (Heteronuclear Single Quantum-Coherence) methods and HMQC (Heteronuclear Multiple Quantum-Coherence) methods.
Hereinafter each of the above methods will be described. In the following description, .sup.1 H combined with .sup.13 C is represented by ".sup.1 H{.sup.13 C}". A radio-frequency magnetic field pulse (RF pulse) that selectively rotate .sup.1 H or .sup.13 C spins through .alpha..degree. with respect to the .beta. axis (.beta.=x, y, pr z) is represented by a ".alpha..degree..beta.(.sup.1 H or .sup.13 C) pulse". The spin--spin coupling constant of .sup.1 H and .sup.13 C is represented by J.
FIG. 1 shows an INEPT pulse sequence, and FIG. 2 shows the state of .sup.1 H spin at time ta after a lapse of time 1/(4J) from the application of a 180.degree.(.sup.13 C) pulse. For .sup.1 H a 90.degree.x(.sup.1 H) pulse, a 180.degree.y(.sup.1 H) pulse and a 90.degree.y(.sup.1 H) pulse are produced in sequence. For .sup.13 C a 180.degree.(.sup.13 C) pulse and a 90.degree.(.sup.13 C) pulse are produced in sequence. The 180.degree.y(.sup.13 C) pulse and the 180.degree.(.sup.13 C) pulse are produced simultaneously. The 90.degree.y(.sup.1 H) pulse and the 90.degree.(.sup.13 C) pulse are produced simultaneously. The time interval between the 90.degree.x(.sup.1 H) pulse and 180.degree.(.sup.13 C) pulse is set to 1/(4J). The time interval between the 180.degree.(.sup.13 C) pulse and 90.degree.y(.sup.1 H) pulse is also set to 1/(4J). FIG. 3 shows a spectrum of data detected from .sup.13 C, which allows various metabolic functions to be diagnosed.
FIG. 4 shows an INEPT pulse sequence which has an additional decoupling pulse produced for .sup.1 H at data acquisition time. FIGS. 5 and 6 show INPET pulse sequences which have additional 180.degree. pulses produced for .sup.1 H and .sup.13 C to rephase their spins. FIG. 7 shows a polarization transfer pulse sequence which has no 180.degree.pulse. Even with a 180.degree. pulse removed, polarization transfer can be made, but its efficiency is low because the .sup.1 H spins are not refocused.
FIG. 8 shows a DEPT pulse sequence, in which a 90.degree.x(.sup.1 H), a 180.degree.x(.sup.1 H) pulse and a .theta..degree.y(.sup.1 H) pulse are produced sequentially for .sup.1 H, and a 90.degree.(.sup.13 C) and a 180.degree.(.sup.13 C) pulse are produced sequentially for .sup.13 C. The 180.degree.x(.sup.1 H) pulse and the 90.degree.(.sup.13 C) pulse are produced simultaneously. The .theta..degree.y(.sup.1 H) pulse and the 180.degree.(.sup.13 C) pulse are produced simultaneously. The time interval between the 90.degree.x(.sup.1 H) pulse and 90.degree.(.sup.13 C) pulse is set to 1/(2J). The time interval between the 90.degree.(.sup.13 C) pulse and .theta..degree.y(.sup.1 H) pulse is also set to 1/(2J).
FIG. 9 shows an HSQC pulse sequence. The INEPT pulse sequence indicated by block A allows polarization transfer to be made. Signals are then observed from .sup.1 H after a single-quantum coherence period t1 for .sup.13 C during which time a chemical shift of .sup.13 C is developed and a reverse-INEPT pulse sequence indicated by block B. Since J coupling is refocused by a 180.degree. pulse at the center of the period t1, only the .sup.13 C chemical shift is developed during the t1 period. Two-dimensional data S(t1, t2) is acquired by repeating the pulse sequence of FIG. 9 while changing the length of the interval t1. By subjecting the resultant data to two-dimensional Fourier transform, such a spectrum distribution .sigma.(.omega..sup.1 H, .omega..sup.13 C) as shown in FIG. 10 is obtained.
FIG. 11 shows an HMQC pulse sequence. In HMQC, signals are observed from .sup.1 H after a lapse of a multiple-quantum coherence period t1 during which time .sup.13 C chemical shift is developed. Data S(t1, t2) is acquired by repeating the pulse sequence of FIG. 11 while changing the length of the period t1. The resultant data is subjected to two-dimensional Fourier transform to produce such a spectrum distribution as shown in FIG. 12.
With the .sup.1 H observation, it is essential to remove water signals.
With the HSQC pulse sequence of FIG. 9, water signals are removed by a CHESS (chemical shift selective) pulse.
An important problem with the HSQC and HMQC methods is to remove water signals. However, the above-described methods cannot remove .sup.1 H in, for example, glucose (CH) which has a chemical shift close to that of .sup.1 H in water.
FIG. 13 shows an HSQC pulse sequence in which gradient magnetic field pulse Gsel for selecting only coherence of .sup.1 H{.sup.13 C} are added in order to remove water signals.
FIGS. 14 and 16 show HMQC pulse sequences which are improved to remove water signals. FIG. 15A shows the state of magnetization of .sup.1 H at time ta after a lapse of 1/(4J) from the 180.degree. (.sup.13 C) pulse in the INEPT sequence of FIGS. 14 and 16. In FIG. 14, the third proton pulse, which is 90.degree. (.sup.1 H) pulse is produced for the X axis, so that .sup.1 H{.sup.12 C} is returned to longitudinal magnetization and water signals are removed as shown in FIG. 15B. In FIG. 16, the third proton pulse, which is 90.degree. (.sup.1 H) pulse, is produced for the Y axis to return .sup.1 H{.sup.13 C} to longitudinal magnetization and preserve the transverse magnetization of .sup.1 H{.sup.12 C}. In this state, a gradient magnetic field pulse pulse is produced to thereby dephase .sup.1 H{.sup.12 C} and remove water signals. After that, a 90.degree. (.sup.1 H) pulse is produced to return .sup.1 H{.sup.13 C} to transverse magnetization and create the multiple-quantum coherence state.
FIG. 17 shows an HMQC pulse sequence in which gradient magnetic field pulse Gselection are added in order to remove single-quantum coherence of water signals and select only multiple-quantum coherence.
In order to use the INEPT, DEPT, HSQC, or HMQC in in vivo magnetic resonance spectroscopy, the localization is essential.
FIG. 18 shows a DEPT pulse sequence combined with a VSE (volume selective excitation) pulse sequence. In the VSE sequence, a 90.degree. selective excitation pulse and a 90.degree. non-selective excitation pulse are combined to put spins outside a region of interest into pseudo-saturation and make forced recovery of spins within the region of interest, thereby providing the localization of three axes.
However, problems associated with the combined use of the VSE sequence and the DEPT sequence are that widely-used apparatuses cannot produce VSE pulses and the precision of localization is reduced by recovery of longitudinal magnetization of .sup.1 H spins outside a region of interest.
FIG. 19 shows a DEPT sequence which was improved by Yeung et al for localization. In this DEPT sequence, the first 90.degree. (.sup.1 H) pulse for .sup.1 H is used as a slice selective pulse, thereby achieving the localization of one axis.
FIG. 20 shows a SZNEPT sequence which was improved by M. Saner et al in localization. In this sequence, two pulses for .sup.1 H are used as slice selective pulses, thereby achieving the localization of two axes.
FIG. 21 shows a DEPT pulse sequence which was improved by Bomsdorf et al for localization. In this DEPT sequence, the first 90.degree. (.sup.1 H) pulse and two 90.degree. (.sup.1 H) pulses resulting from division of a 180.degree. (.sup.1 H) pulse are used as slice selective pulses to achieve the localization of three axes.
In addition, the combined use of an ISIS (image selected in vivo spectroscopy) technique and the DEPT sequence is also being considered for localization. However, this method requires two data acquisition steps for one-dimensional localization and eight data acquisition steps for three-dimensional localization. This requires a long observation time. Further, this method also has a problem that the precision of localization is reduced by recovery of longitudinal magnetization.
FIG. 22 shows an HMQC sequence intended to achieve the localization of one axis by using a 90.degree. (.sup.1 H) pulse for .sup.1 H as a slice selective pulse.
As described above, the INEPT, DEPT, HSQC, and HMQC methods have difficulties in achieving efficient localization.
In addition, the .sup.1 H observation methods (HSQC, HMQC) have a problem that water signals cannot be successfully removed.
FIG. 23 shows changes of the spectrum of the brain of a monkey with time after glucose in which .sup.13 C is labeled with carbon is injected into its vein. The area of this spectrum corresponds to the amount of metabolite. As shown in FIG. 24, by observing changes of the area of the spectrum with time, information is obtained which is useful for diagnosis of metabolic speed by way of example. The area of the spectrum was calculated on the basis of an approximate curve of the spectrum curve. However, the precision of the approximate curve was too low to obtain useful information with high precision.